Fda's Final Rule on Laboratory Developed Tests as Medical Devices: an Overview and Where Legal Counsel Should Focus

• Citation: Vol. 4 No. 3
• Publication year: 2024

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Megan Robertson, James Boiani, and Robert Wanerman ^*

Abstract: On May 6, 2024, following over a decade of discourse, the FDA officially published its long-awaited "Medical Devices; Laboratory Developed Tests" Final Rule. The LDT Final Rule formalized the FDA's position that in the future the Agency will actively regulate LDTs as medical devices, ending the historical enforcement discretion for such tests. While there have already been legal and regulatory challenges to the FDA's authority to issue this Final Rule, advisors to stakeholders in the laboratory industry, and life sciences businesses in general, should familiarize themselves with the key aspects of this LDT Final Rule and assess the impact it may have on their future operations.

Introduction

Ask any laboratory stakeholder for their opinion on the hot topic of 2024 and the response will likely be the same across the board—laboratory developed tests (LTDs). Laboratory developed tests, or LDTs, are a category of in vitro diagnostic tests (IVDs) that, until recently, have been subject to "enforcement discretion" by the U.S. Food and Drug Administration (FDA or the Agency). This means that, historically, the FDA has not imposed the same pre-market regulatory obligations on LDTs so long as they are designed, manufactured, and used within a single laboratory that holds a high-complexity certification through the federal Clinical

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Laboratory Improvement Amendments (CLIA) program. While IVDs are considered medical devices subject to FDA regulation, including pre-market approval, for decades the Agency has allowed LDTs to be marketed without pre-market approval so long as they did not raise safety concerns.

This all changed on May 6, 2024, when, following over ten years of discourse, the FDA officially published its long-awaited "Medical Devices; Laboratory Developed Tests" Final Rule (the Final Rule). ¹ The Final Rule formalized the FDA's position that in the future the Agency will actively regulate LDTs as medical devices, ending the tenure of enforcement discretion for such tests.

LDT History Overview

Those outside of the laboratory industry may wonder what sparked such a change. From the FDA's point of view, the risk analysis of LDTs has changed due in part to the evolution of the LDT landscape as a whole. Many labs started to integrate hightech and complex instrumentation, as well as software, into the traditional LDTs. Labs also started to engage third parties for tasks that historically had been performed "in house," such as a specimen collection. Availability of LDTs expanded, increasing the volume of specimens run by the single lab offering the LDT FDA also points to LDTs that are manufactured with components that are not intended for clinical use, but are still used to inform clinical treatment, screen, predict risk, and diagnose patients. As FDA states in the Final Rule, "[t]he risks associated with most LDTs today are therefore much greater," and there is concern that "firms are offering IVDs as 'LDTs' even when they are not LDTs as defined on FDA's website, because they are not actually designed, manufactured, and used within a single laboratory."

Previously, the FDA periodically addressed these concerns by issuing warning letters stating that certain types of tests, such as direct-to-consumer LDTs ² and certain pharmacogenomic LDTs, ³ were carved out of its enforcement discretion policy for LDTs (to the undoubted surprise of some labs). Sometimes the FDA has issued guidance documents attempting to do the same. Most notably, a 2007 draft guidance on IVD multivariate index assays

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(MIAs) indicated that LDTs that were incorporating certain MIA software algorithms were not considered within the scope of the LDTs subject to the FDA's enforcement discretion. ⁴ Despite this, "dry lab" algorithmic tests have proliferated under the LDT framework and are now an integral part of medicine. ⁵ At other times, the FDA has addressed concerns regarding certain LDTs in other ways, such as pressuring manufacturers to address how the test components they sell are being used by lab customers, or relying on its jurisdiction over products that are used with the test but are not the test itself, such as sample transport and collection kits being distributed outside the lab (and thus not used solely "within a single lab") to restrict the use of these tests. ⁶

Based on this muddled history, the regulatory status of LDTs and companies' decisions regarding their development and use have been clouded by uncertainty and have demanded some measure of risk tolerance.

There have also been prior attempts by both the FDA and Congress to offer clarity by creating new regulatory frameworks. The FDA's most notable and comprehensive attempt before the Final Rule was its 2014 initiative that sought to develop a regulatory framework through FDA guidance under its existing authorities, applying a risk-based regulatory structure...